1.Pivotal Role of Subcortical Structures as a Network Hub in Focal Epilepsy: Evidence from Graph Theoretical Analysis Based on Diffusion-Tensor Imaging.
Kang Min PARK ; Byung In LEE ; Kyong Jin SHIN ; Sam Yeol HA ; JinSe PARK ; Si Eun KIM ; Sung Eun KIM
Journal of Clinical Neurology 2019;15(1):68-76
BACKGROUND AND PURPOSE: There is accumulating evidence that epilepsy is caused by network dysfunction. We evaluated the hub reorganization of subcortical structures in patients with focal epilepsy using graph theoretical analysis based on diffusion-tensor imaging (DTI). In addition, we investigated differences in the values of diffusion tensors and scalars, fractional anisotropy (FA), and mean diffusivity (MD) of subcortical structures between patients with focal epilepsy and healthy subjects. METHODS: One hundred patients with focal epilepsy and normal magnetic resonance imaging (MRI) findings and 80 age- and sex-matched healthy subjects were recruited prospectively. All subjects underwent DTI to obtain data suitable for graph theoretical analysis. We investigated the differences in the node strength, cluster coefficient, eigenvector centrality, page-rank centrality measures, FA, and MD of subcortical structures between patients with epilepsy and healthy subjects. RESULTS: After performing multiple corrections, the cluster coefficient and the eigenvector centrality of the globus pallidus were higher in patients with epilepsy than in healthy subjects (p=0.006 and p=0.008, respectively). In addition, the strength and the page-rank centrality of the globus pallidus tended to be higher in patients with epilepsy than in healthy subjects (p=0.092 and p=0.032, respectively). The cluster coefficient of the putamen was lower in patients with epilepsy than in healthy subjects (p=0.004). The FA values of the caudate nucleus and thalamus were significantly lower in patients with epilepsy than in healthy subjects (p=0.009 and p=0.007, respectively), whereas the MD value of the thalamus was higher than that in healthy subjects (p=0.005). CONCLUSIONS: We discovered the presence of hub reorganization of subcortical structures in focal epilepsy patients with normal MRI findings, suggesting that subcortical structures play a pivotal role as a hub in the epilepsy network. These findings further reinforce the idea that epilepsy is a network disease.
Anisotropy
;
Caudate Nucleus
;
Connectome
;
Diffusion
;
Epilepsies, Partial*
;
Epilepsy
;
Globus Pallidus
;
Healthy Volunteers
;
Humans
;
Magnetic Resonance Imaging
;
Prospective Studies
;
Putamen
;
Thalamus
2.Effect of Single-Nucleotide Polymorphisms on Decline of Dopamine Transporter Availability in Parkinson's Disease.
Seunghyeon SHIN ; Keunyoung KIM ; Jae Meen LEE ; Eun Joo KIM ; Seong Jang KIM ; In Joo KIM ; Kyoungjune PAK ; Myung Jun LEE
Journal of Clinical Neurology 2019;15(1):102-107
BACKGROUND AND PURPOSE: We aimed to determine the association between the annual changes in dopamine transporter (DAT) availability as measured by 123I-ioflupane (123I-FP-CIT) single-photon-emission computed tomography and single-nucleotide polymorphisms (SNPs) known to be risk factors in Parkinson's disease (PD). METHODS: In total, 150 PD patients were included from the Parkinson's Progression Markers Initiative database. Specific SNPs that are associated with PD were selected for genotyping. SNPs that were not in Hardy-Weinberg equilibrium or whose minor allele frequency was less than 0.05 were excluded. Twenty-three SNPs met the inclusion criteria for this study. The Kruskal-Wallis test was used to compare annual percentage changes in DAT availability for three subgroups of SNP. RESULTS: None of the 23 SNPs exerted a statistically significant effect (p < 0.0022) on the decline of DAT availability in PD patients. However, we observed trends of association (p < 0.05) between three SNPs of two genes with the annual percentage change in DAT availability: 1) rs199347 on the putamen (p=0.0138), 2) rs356181 on the caudate nucleus (p=0.0105), and 3) rs3910105 on the caudate nucleus (p=0.0374). A post-hoc analysis revealed that DAT availability was reduced the most for 1) the putamen in the CC genotype of rs199347 (vs. CT, p=0.0199; vs. TT, p=0.0164), 2) the caudate nucleus in the TT genotype of rs356181 (vs. CC, p=0.0081), and 3) the caudate nucleus in the CC genotype of rs3910105 (vs. TT, p=0.0317). CONCLUSIONS: Significant trends in the associations between three SNPs and decline of DAT availability in PD patients have been discovered.
Caudate Nucleus
;
Dopamine Plasma Membrane Transport Proteins*
;
Dopamine*
;
Gene Frequency
;
Genotype
;
Humans
;
Parkinson Disease*
;
Polymorphism, Single Nucleotide
;
Putamen
;
Risk Factors
;
Tomography, Emission-Computed, Single-Photon
3.Utility of white matter to gray matter signal intensity ratio in comatose patients treated by targeted temperature management after cardiac arrest: a preliminary study
Kyoung Tak KEUM ; Yong Hwan KIM ; Seong Youn HWANG ; Jun Ho LEE ; Dong Woo LEE ; Yun Gyu SONG ; Jung Hwa LEE ; Kyoung Yul LEE
Journal of the Korean Society of Emergency Medicine 2019;30(5):437-445
OBJECTIVE: This study examined the efficacy of the white matter (WM) to gray matter (GM) signal intensity ratio (SIR) in predicting the clinical prognosis of cardiac arrest patients. METHODS: Thirty-one patients who were resuscitated from cardiac arrest and underwent brain magnetic resonance imaging (MRI) were investigated retrospectively. Thirty one subjects with normal brain MRI findings served as the controls. The signal intensities (SI) were measured on T2-weighted image (T2WI). The circular regions of measurement (2–10 mm²) were placed over the regions of interest, and the average signals in GM and WM were recorded in the caudate nucleus (CN), putamen, anterior limb of the internal capsule, corpus callosum (CC), and in the cortex and WM of the frontal lobe. Cerebral performance category (CPC) 1–2 were classified as a good prognosis, and CPC 3–5 were classified as a poor prognosis. RESULTS: Most combinations of the SIR of WM to GM and most SIs of GM, except the frontal cortex, were significantly different between the two groups. On the other hand, the SI of WM was insignificant between both groups. In receiver operating characteristic (ROC) curve analysis, the SIR of the CC to CN had an area under the ROC curve (AUROC) of 1.00 for a cut-off value of 1.59 (sensitivity, 100%; specificity, 100%), the SIR of the CC to putamen had also an AUROC of 1.00 for a cut-off value of 1.43 (sensitivity, 100%; specificity, 100%). CONCLUSION: The SIR of WM to GM measured on a T2WI is related to the neurological outcome after a cardiac arrest.
Brain
;
Caudate Nucleus
;
Coma
;
Corpus Callosum
;
Extremities
;
Frontal Lobe
;
Gray Matter
;
Hand
;
Heart Arrest
;
Humans
;
Internal Capsule
;
Magnetic Resonance Imaging
;
Prognosis
;
Putamen
;
Retrospective Studies
;
ROC Curve
;
Sensitivity and Specificity
;
White Matter
4.Association Between Duration of Dysphagia Recovery and Lesion Location on Magnetic Resonance Imaging in Patients With Middle Cerebral Artery Infarction
Jae Ho KIM ; Se Hyun OH ; Ho Joong JEONG ; Young Joo SIM ; Dung Gyu KIM ; Ghi Chan KIM
Annals of Rehabilitation Medicine 2019;43(2):142-148
OBJECTIVE: To investigate association between lesion location on magnetic resonance imaging (MRI) performed after an infarction and the duration of dysphagia in middle cerebral artery (MCA) infarction. METHODS: A videofluoroscopic swallowing study was performed for 59 patients with dysphagia who were diagnosed as cerebral infarction of the MCA territory confirmed by brain MRI. Lesions were divided into 11 regions of interest: primary somatosensory cortex, primary motor cortex, supplementary motor cortex, anterior cingulate cortex, orbitofrontal cortex, parieto-occipital cortex, insular cortex, posterior limb of the internal capsule (PLIC), thalamus, basal ganglia (caudate nucleus), and basal ganglia (putamen). Recovery time was defined as the period from the first day of L-tube feeding to the day that rice porridge with thickening agent was prescribed. Recovery time and brain lesion patterns were compared and analyzed. RESULTS: The mean recovery time of all patients was 26.71±16.39 days. The mean recovery time was 36.65±15.83 days in patients with PLIC lesions and 32.6±17.27 days in patients with caudate nucleus lesions. Only these two groups showed longer recovery time than the average recovery time for all patients. One-way analysis of variance for recovery time showed significant differences between patients with and without lesions in PLIC and caudate (p<0.001). CONCLUSION: Injury to both PLIC and caudate nucleus is associated with longer recovery time from dysphagia.
Basal Ganglia
;
Brain
;
Caudate Nucleus
;
Cerebral Cortex
;
Cerebral Infarction
;
Deglutition
;
Deglutition Disorders
;
Extremities
;
Gyrus Cinguli
;
Humans
;
Infarction
;
Infarction, Middle Cerebral Artery
;
Internal Capsule
;
Magnetic Resonance Imaging
;
Middle Cerebral Artery
;
Motor Cortex
;
Prefrontal Cortex
;
Somatosensory Cortex
;
Thalamus
5.Discovery of a new division system in brain and the regionalized drainage route of brain interstitial fluid.
Journal of Peking University(Health Sciences) 2019;51(3):397-401
Brain extracellular space (ECS) is a narrow, irregular space, which provides immediate living environment for neural cells and accounts for approximately 15%-20% of the total volume of living brain. Twenty-five years ago, as an interventional radiologist, the author was engaged in investigating early diagnosis and treatment of cerebral ischemic stroke, and the parameters of brain ECS was firstly derived and demonstrated during the study of the permeability of blood-brain barrier (BBB) and its diffusion changes in the cerebral ischemic tissue. Since then, the author and his team had been working on developing a novel measuring method of ECS: tracer-based magnetic resonance imaging (MRI), which could measure brain ECS parameters in the whole brain scale and make the dynamic drainage process of the labelled brain interstitial fluid (ISF) visualized. By using the new method, the team made a series of new findings about the brain ECS and ISF, including the discovery of a new division system in the brain, named regionalized ISF drainage system. We found that the ISF drainage in the deep brain was regionalized and the structural and functional parameters in different interstitial system (ISS) divisions were disparate. The ISF in the caudate nucleus could be drained to ipsilateral cortex and finally into the subarachnoid space, which maintained the pathway of ISF-cerebrospinal fluid (CSF) exchange. However, the ISF in the thalamus was eliminated locally in its anatomical division. After verifying the nature of the barrier structure between different drainage divisions, the author proposed the hypothesis of "regionalized brain homeostasis". Thus, we demonstrated that the brain was protected not only by the BBB, which avoided potential exogenous damage through the vascular system, but was also protected by an internal ISF drainage barrier to avoid potentially harmful interference from other ECS divisions in the deep brain. With the new findings and the proposed hypothesis, an innovative therapeutic method for the treatment of encephalopathy with local drug delivery via the brain ECS pathway was established. By using this new administration method, the drug was achieved directly to the space around neurons or target regions, overwhelming the impendence from the blood-brain barrier, thus solved the obstacles of low efficiency in traditional drug investigation. At present, new methods and discoveries developed by the author and his team have been widely applied in several frontier fields including neuroscience, new drug research and development, neurodevelopment aerospace medicine, clinical encephalopathy treatment,new neural network modeling and so on.
Brain
;
Caudate Nucleus
;
Extracellular Fluid
;
Extracellular Space
;
Magnetic Resonance Imaging
6.Regional Brain Activity During Rest and Gastric Water Load in Subtypes of Functional Dyspepsia: A Preliminary Brain Functional Magnetic Resonance Imaging Study
Yanwen CHEN ; Ruifeng WANG ; Bo HOU ; Feng FENG ; Xiucai FANG ; Liming ZHU ; Xiaohong SUN ; Zhifeng WANG ; Meiyun KE
Journal of Neurogastroenterology and Motility 2018;24(2):268-279
BACKGROUND/AIMS: Functional dyspepsia (FD) remains a great clinical challenge since the FD subtypes, defined by Rome III classification, still have heterogeneous pathogenesis. Previous studies have shown notable differences in visceral sensation processing in the CNS in FD compared to healthy subjects (HS). However, the role of CNS in the pathogenesis of each FD subtype has not been recognized. METHODS: Twenty-eight FD patients, including 10 epigastric pain syndrome (EPS), 9 postprandial distress syndrome (PDS), and 9 mixed-type, and 10 HS, were enrolled. All subjects underwent a proximal gastric perfusion water load test and the regional brain activities during resting state and water load test were investigated by functional magnetic resonance imaging. RESULTS: For regional brain activities during the resting state and water load test, each FD subtype was significantly different from HS (P < 0.05). Focusing on EPS and PDS, the regional brain activities of EPS were stronger than PDS in the left paracentral lobule, right inferior frontal gyrus pars opercularis, postcentral gyrus, precuneus, insula, parahippocampal gyrus, caudate nucleus, and bilateral cingulate cortices at the resting state (P < 0.05), and stronger than PDS in the left inferior temporal and fusiform gyri during the water load test (P < 0.05). CONCLUSIONS: Compared to HS, FD subtypes had different regional brain activities at rest and during water load test, whereby the differences displayed distinct manifestations for each subtype. Compared to PDS, EPS presented more significant differences from HS at rest, suggesting that the abnormality of central visceral pain processing could be one of the main pathogenesis mechanisms for EPS.
Brain
;
Broca Area
;
Caudate Nucleus
;
Classification
;
Dyspepsia
;
Functional Neuroimaging
;
Healthy Volunteers
;
Humans
;
Magnetic Resonance Imaging
;
Parahippocampal Gyrus
;
Parietal Lobe
;
Perfusion
;
Prefrontal Cortex
;
Sensation
;
Somatosensory Cortex
;
Visceral Pain
;
Water
7.Non-Motor Symptom Burdens Are Not Associated with Iron Accumulation in Early Parkinson's Disease: a Quantitative Susceptibility Mapping Study.
Chaewon SHIN ; Seon LEE ; Jee Young LEE ; Jung Hyo RHIM ; Sun Won PARK
Journal of Korean Medical Science 2018;33(13):e96-
BACKGROUND: Quantitative susceptibility mapping (QSM) has been used to measure iron accumulation in the deep nuclei of patients with Parkinson's disease (PD). This study examined the relationship between non-motor symptoms (NMSs) and iron accumulation in the deep nuclei of patients with PD. METHODS: The QSM data were acquired from 3-Tesla magnetic resonance imaging (MRI) in 29 patients with early PD and 19 normal controls. The Korean version of the NMS scale (K-NMSS) was used for evaluation of NMSs in patients. The patients were divided into high NMS and low NMS groups. The region-of-interest analyses were performed in the following deep nuclei: red nucleus, substantia nigra pars compacta, substantia nigra pars reticulata, dentate nucleus, globus pallidus, putamen, and head of the caudate nucleus. RESULTS: Thirteen patients had high NMS scores (total K-NMSS score, mean = 32.1), and 16 had low NMS scores (10.6). The QSM values in the deep were not different among the patients with high NMS scores, low NMS scores, and controls. The QSM values were not correlated linearly with K-NMSS total score after adjusting the age at acquisition of brain MRI. CONCLUSION: The study demonstrated that the NMS burdens are not associated with iron accumulation in the deep nuclei of patients with PD. These results suggest that future neuroimaging studies on the pathology of NMSs in PD should use more specific and detailed clinical tools and recruit PD patients with severe NMSs.
Basal Ganglia
;
Brain
;
Caudate Nucleus
;
Cerebellar Nuclei
;
Globus Pallidus
;
Head
;
Humans
;
Iron*
;
Magnetic Resonance Imaging
;
Neuroimaging
;
Parkinson Disease*
;
Pars Compacta
;
Pars Reticulata
;
Pathology
;
Putamen
;
Red Nucleus
8.Effect of rs3910105 in the Synuclein Gene on Dopamine Transporter Availability in Healthy Subjects.
Youngduk SEO ; Kyoungjune PAK ; Hyun Yeol NAM ; Ju Won SEOK ; Myung Jun LEE ; Eun Joo KIM ; Jae Meen LEE ; Seong Jang KIM ; In Joo KIM
Yonsei Medical Journal 2018;59(6):787-792
PURPOSE: The present study investigated associations between dopamine transporter (DAT) availability and α-synuclein levels in cerebrospinal fluid, as well as synuclein gene (SNCA) transcripts, and the effect of single nucleotide polymorphism of SNCA on DAT availability in healthy subjects. MATERIALS AND METHODS: The study population comprised healthy controls who underwent 123I-FP-CIT single-photon emission computed tomography screening. Five SNCA probes were used to target the boundaries of exon 3 and exon 4 (SNCA-E3E4), transcripts with a long 3′UTR region (SNCA-3UTR-1, SNCA-3UTR-2), transcripts that skip exon 5 (SNCA-E4E6), and the rare short transcript isoforms that comprise exons 1–4 (SNCA-007). RESULTS: In total, 123 healthy subjects (male 75, female 48) were included in this study. DAT availability in the caudate nucleus (p=0.0661) and putamen (p=0.0739) tended to differ according to rs3910105 genotype. In post-hoc analysis, DAT availability in the putamen was lower in subjects of TT genotype than those of CC/CT (p=0.0317). DAT availability in the caudate nucleus also showed a trend similar to that in the putamen (p=0.0597). Subjects of CT genotype with rs3910105 showed negative correlations with DAT availability in the putamen with SNCA-E3E4 (p=0.037, rho=−0.277), and SNCA-E4E6 (p=0.042, rho=−0.270), but not those of CC/TT genotypes. CONCLUSION: This is the first study to investigate the association of rs3910105 in SNCA with DAT availability. rs3910105 had an effect on DAT availability, and the correlation between DAT availability and SNCA transcripts were significant in CT genotypes of rs3910105.
Biomarkers
;
Caudate Nucleus
;
Cerebrospinal Fluid
;
Dopamine Plasma Membrane Transport Proteins*
;
Dopamine*
;
Exons
;
Female
;
Genotype
;
Healthy Volunteers*
;
Humans
;
Mass Screening
;
Polymorphism, Single Nucleotide
;
Protein Isoforms
;
Putamen
;
Synucleins*
;
Tomography, Emission-Computed
9.Consolidation of a Learned Skill Correlates with Dopamine SPECT Uptake in Early Parkinson's Disease.
Nicolas NICASTRO ; Aurélie L MANUEL ; Valentina GARIBOTTO ; Pierre R BURKHARD ; Armin SCHNIDER
Journal of Clinical Neurology 2018;14(4):505-512
BACKGROUND AND PURPOSE: Basal ganglia play a pivotal role in procedural memory. However, the correlation between skill learning and striatal 123I-ioflupane uptake in Parkinson's disease (PD) has not been reported previously. Our objective was to determine whether visuomotor skill learning is associated with striatal 123I-ioflupane uptake in early PD. METHODS: We designed a case–control study to assess learning and consolidation of a visuomotor learning task (mirrored drawing of star-shaped figures) performed on two consecutive days by early-PD patients (disease duration < 2 years) and age-matched healthy subjects. Outcomes were the error rate and time per trial, as well as performance indices to assess the relative improvement on the first day (learning) and the retention on the second day (consolidation). For PD patients, we evaluated the correlation of skill learning with semiquantitative 123I-ioflupane uptake. RESULTS: We included 9 PD patients and 10 control subjects with the same baseline characteristics (age, male/female ratio, educational level, Mini Mental State Examination score, and Hospital Anxiety and Depression Scale score, all p>0.18) other than the score on part III of the Movement Disorders Society Unified Parkinson's Disease Rating Scale, which was higher in the PD patients (mean±SD: 15.0±10.4 vs. 1.3±1.1, p < 0.001). The learning indices were the same in the two groups (p>0.5), whereas PD patients showed a lower consolidation index for the time per trial (p=0.009). Moreover, this performance was correlated with uptake in the right caudate nucleus (Spearman's rho=0.82, p=0.007) and the right striatum (Spearman's rho=0.67, p=0.049), including when multiple linear regression adjusting for the levodopa equivalent daily dose was performed (p=0.005 for the caudate nucleus and p=0.024 for the striatum). CONCLUSIONS: This study provides evidence of a correlation between procedural memory impairment and striatal dopaminergic dysfunction in early PD.
Anxiety
;
Basal Ganglia
;
Caudate Nucleus
;
Cognition
;
Depression
;
Dopamine*
;
Healthy Volunteers
;
Humans
;
Learning
;
Levodopa
;
Linear Models
;
Memory
;
Movement Disorders
;
Parkinson Disease*
;
Tomography, Emission-Computed, Single-Photon*
10.Application of anoptomagnetic probe Gd-DO3A-EA-FITC in imaging and analyzing the brain interstitial space.
Yun Qian LI ; Hui SHENG ; Lei LIANG ; Yue ZHAO ; Huai Ye LI ; Ning BAI ; Tong WANG ; Lan YUAN ; Hong Bin HAN
Journal of Peking University(Health Sciences) 2018;50(2):221-225
OBJECTIVE:
To investigate the application of the optical magnetic bimodal molecular probe Gd-DO3A-ethylthiouret-fluorescein isothiocyanate (Gd -DO3A-EA-FITC) in brain tissue imaging and brain interstitial space (ISS).
METHODS:
In the study, 24 male SD rats were randomly divided into 3 groups, including magnetic probe group (n=6), optical probe group (n=6) and optical magnetic bimodal probe group (n=12), then the optical magnetic bimodal probe group was divided equally into magnetic probe subgroup (n=6) and optical probe subgroup (n=6). Referencing the brain stereotaxic atlas, the coronal globus pallidus as center level, the probes including gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), fluorescein isothiocyanate (FITC) and Gd-DO3A-EA-FITC of 2 μL (10 mmol/L) were injected into the caudate nucleus respectively, magnetic resonance imaging (MRI) was performed in the magnetic probe group and magnetic probe subgroup to image the dynamic diffusion and distribution of the probes in the brain ISS, a self-developed brain ISS image processing system was used to measure the diffusion coefficient, clearance, volume fraction and half-time in these two groups. Laser scanning confocal microscope (LSCM) was performed in vitro in the optical probe group and optical probe subgroup for fluorescence imaging at the time points 2 hours after the injection of the probe, and the distribution in the oblique sagittal slice was compared with the result of the first two groups.
RESULTS:
For the magnetic probe group and magnetic probe subgroup, there were the same imaging results between the probes of Gd-DTPA and Gd-DO3A-EA-FITC. The diffusion parameters of Gd-DTPA and Gd-DO3A-EA-FITC were as follows: the average diffusion coefficients [(3.31±0.11)×10-4 mm2/s vs. (3.37±0.15)×10-4 mm2/s, t=0.942, P=0.360], the clearance [(3.04±0.37) mmol/L vs. (2.90±0.51) mmol/L, t=0.640, P=0.531], the volume fractions (17.18%±0.14% vs. 17.31%±0.15%, t=1.961, P=0.068), the half-time [(86.58±3.31) min vs. (84.61±2.38) min, t=1.412, P=0.177], the diffusion areas [(23.25±0.68) mm2 vs. (22.71±1.00) mm2, t=1.100, P=0.297]. The statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant. Moreover, for the optical probe group and optical probe subgroup, the diffusion area of Gd-DO3A-EA-FITC [(22.61±1.16) mm2] was slightly larger than that of FITC [(22.10±1.29) mm2], the statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant (t=0.713, P=0.492).
CONCLUSION
Gd-DO3A-EA-FITC shows the same imaging results as the traditional GD-DTPA, and it can be used in measuring brain ISS.
Animals
;
Brain/diagnostic imaging*
;
Caudate Nucleus
;
Contrast Media
;
Diffusion
;
Fluorescein-5-isothiocyanate
;
Fluorescence
;
Gadolinium DTPA
;
Imaging, Three-Dimensional
;
Magnetic Resonance Imaging
;
Male
;
Microscopy, Confocal
;
Molecular Probes
;
Rats
;
Rats, Sprague-Dawley

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